Therapy to Improve Wound Healing with DNA Expression Vector for HIF 11 and Electroporation Impaired wound healing is a tremendous problem for individuals with diabetes. Patients with diabetes are at risk for developing foot ulcers. These non-healing ulcerations on the foot are disabling, and their progression leads to amputation of the lower extremity. Diabetes is the most frequent cause for lower extremity amputation in the United States. Based on a decade of research at Johns Hopkins University, Canton Biotechnologies Inc has been created to develop a technology with potential for improving wound healing in diabetic individuals. This technology is based on expressing an oxygen resistant, highly active form of the transcription factor Hypoxia Inducible Factor 11 (CA5-HIF). The approach is based on electroporation (EP) mediated delivery of a DNA expression vector encoding CA5-HIF to the wound. Using a research grade EP device, we have demonstrated sustained expression of HIF after CA5 transfection, resulting in up- regulation of mRNA expression for important angiogenic peptides including VEGF, PLGF, PDGF-B, Angiopoietin 1 and Angiopoietin 2. Pre-clinical testing in diabetic mice with excisional wounds has demonstrated that EP mediated delivery of CA5-HIF into wounds can significantly improve angiogenesis and overall wound healing in a model of diabetic ulceration. Having secured the license to CA5 for use in wound healing applications from JHU, Canton is now positioning the product for advancement into clinical development. Towards this end, the company has evaluated EP based delivery systems suitable for use in the clinical setting. These efforts have culminated in a partnership with Ichor Medical Systems, Inc. to access the company's EP technology for delivery of the CA5 DNA. By providing a "clinic ready" EP technology with a substantial database of pre-clinical and clinical usage, this agreement will greatly facilitate the development of the CA5 product. Building on the promising pre-clinical data generated to date, the objective of the proposed STTR program is to bring the CA5 product candidate into clinical testing. The program for the STTR project is based on informal guidance from FDA CBER that was obtained by Canton. The FDA letter specifies the scope and nature of the initial pre- clinical proof of concept including demonstration of efficacy, biodistribution and toxicity in the diabetic mouse model. Specifically, STTR Phase 1 will comprise additional pre- clinical testing conducted by Canton researchers to further characterize the safety and efficacy of CA5 delivery in the murine model of wound healing using the Ichor "clinic ready" EP device. PUBLIC HEALTH RELEVANCE: Therapy to Improve Wound Healing with DNA Expression Vector for HIF 11 and Electroporation Impaired wound healing is a tremendous problem for individuals with diabetes. Patients with diabetes are at risk for developing foot ulcers. These non-healing ulcerations on the foot are disabling, and their progression leads to amputation of the lower extremity. Diabetes is the most frequent cause for lower extremity amputation in the United States. Based on a decade of research at Johns Hopkins University, Canton Biotechnologies Inc has been created to develop a technology with potential for improving wound healing in diabetic individuals. The approach is based on electroporation (EP) mediated delivery of a DNA expression vector encoding CA5-HIF to the wound. These efforts have culminated in a partnership with Ichor Medical Systems, Inc. to access the company's "clinic ready" EP device for delivery of the CA5 DNA. Building on the promising pre- clinical data generated to date, the objective of the proposed STTR program is to bring the CA5 product candidate into clinical testing.